The genetic mechanisms governing hematopoietic differentiation in normal and leukemic erythroid and myeloid cells are being studied through use of cell lines which contain markers of human hematopoietic differentiation. Hybrid mouse erythroleukemia cell lines which contain the chromosome bearing the human alpha globin genes as the only human chromosome have been derived using human donor cells which differ with respect to their epigenotype, stages of development and genetic composition. A series of such hybrid cells, each containing human alpha globin genes from patients in whom non-deletion mutations have led to altered alpha globin gene expression, has been constructed. The various steps of gene expression are being characterized using Southern and northern nucleic acid transfers as well as 2 dimensional gel chromotography of non-histone chromosomal proteins. Similar techniques are being applied to HL60, a continuously proliferating human promyelocytic leukemia cell line, in hopes of understanding the regulation of markers of monocyte and of myeloid differentiation in these human leukemia cells, as well as the process which governs commitment to normal maturation in normal cells which is defective in the HL60 cells.